A Common Pharmacophoric Footprint for AIDS Vaccine Design

The most promising target antigen for an HIV vaccine designed using the classic antibody
strategy has been the viral coat protein gp120. Unfortunately, its high variability has prevented
this approach. We examine here a 15-residue peptide derived from the CD4-binding domain of
gp120. By use of molecular dynamics computer simulation, it is shown that despite considerable
sequence variation, the three-dimensional structure of the peptide is preserved over the full
range of clade-specific sequences. Furthermore, sequences threaded onto the structure exhibit
common three-dimensional electrostatic and hydrophobic properties. These common physicochemical characteristics constitute a pharmacophoric footprint that promises to be useful in
the design of a synthetic antigen for vaccine development.